Development of Dual Inhibitors against Alzheimer's Disease Using Fragment-Based QSAR and Molecular Docking
By M. Goyal, J. Dhanjal, Sukriti Goyal, C. Tyagi, R. Hamid, A. Grover. 2014
41 citations recorded by the source corpus.
Alzheimer's (AD) is the leading cause of dementia among elderly people. Considering the complex heterogeneous etiology of AD, there is an urgent need to develop multitargeted drugs for its suppression. β-amyloid cleavage enzyme (BACE-1) and acetylcholinesterase (AChE), being important for AD progression, have been considered as promising drug targets. In this study, a robust and highly predictive group-based QSAR (GQSAR) model has been developed based on the descriptors calculated for the fragments of 20 1,4-dihydropyridine (DHP) derivatives. A large combinatorial library of DHP analogues was created, the activity of each compound was predicted, and the top compounds were analyzed using refined molecular docking. A detailed interaction analysis was carried out for the top two compounds (EDC and FDC) which showed significant binding affinity for BACE-1 and AChE. This study paves way for consideration of these lead molecules as prospective drugs for the effective dual inhibition of BACE-1 and AChE. The GQSAR model provides site-specific clues about the molecules where certain modifications can result in increased biological activity. This information could be of high value for design and development of multifunctional drugs for combating AD.
Subfields: Computational Theory and Mathematics, Organic Chemistry, Pharmacology, Computational Chemistry & Drug Discovery
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In Computational Theory and Mathematics
In Organic Chemistry
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Citations in the corpus
- A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets (2015, methodology): “The β -amyloid cleavage enzyme BACE-1 and acetylcholinesterase (AChE) were recently studied using a group-based QSAR approach to designing fragments (48).”